Dr. Bakshi is an assistant professor of neurology at Buffalo. During 1991 to 1996, he completed an internship at Massachusetts General Hospital, followed by neurology residency at UCLA and neuroimaging fellowship at Buffalo. His immediate goal is to .perform clinical-neuroimaging correlation research concentrating on multiple sclerosis (MS). His long- term career goal is to obtain the skills and experience necessary to develop into a funded independent clinical investigator using neuroimaging to study the pathophysiology of MS. The proposed three- year research training will provide skills for him in important aspects of patient-oriented research in MS. He will deepen his knowledge of biostatistics and epidemiology through formal coursework and supervision. He will learn a variety of computer-assisted MRI analysis methods under the teaching of Dr. Jack Simon that are critical in assessing MS. He will learn how to correlate these data with clinical and neuropathologic findings under the guidance of Dr. Lawrence Jacobs. Dr. Bakshi proposes to study MRI T2 shortening - "Black T2" (BT2) - as a surrogate marker of brain injury in MS. He will extend and attempt to confirm his preliminary observations that BT2 is present commonly in deep central gray matter as compared to normal controls by measuring tissue intensities and T2 relaxation times. He will determine if BT2 varies over time in parallel with other MRI changes (plaques/atrophy), clinical evolution, and therapeutic effects by analyzing 2-year longitudinal data of interferon-beta vs. placebo treated MS patients. To evaluate the hypothesis that BT2 represents pathologic iron deposition, Dr. Bakshi will examine autopsied MS brains in collaboration with Dr. Peter Ostrow for microscopic iron deposition. If the current study is fruitful, BT2 could become a useful laboratory marker of disease burden to assess the course of disease, select patients for therapies, or measure immunotherapeutic effects. In future studies, BT2 can be correlated with metabolism and MR spectroscopic evidence of neuronal injury in deep gray matter. If iron plays a pathophysiologic role in MS, this could offer a novel therapeutic opportunity. Alternatively, if iron accumulation is a disease epiphenomenon, then BT2 could be used as a noninvasive marker of brain degeneration.